Healthcare Industry News: Ortho Biotech
News Release - May 31, 2008
VELCADE(R) (Bortezomib) for Injection Based Treatment Delivers Impressive Complete Response and Survival in Patients With Newly Diagnosed Multiple MyelomaIFM presents updated results from Phase III clinical trial
CHICAGO, May 31 (HSMN NewsFeed) -- Millennium Pharmaceuticals, The Takeda Oncology Company, today announced the presentation of updated results from a 482 patient, multi-center, randomized Phase III clinical trial, comparing VELCADE and dexamethasone (VcD) to vincristine, adriamycin and dexamethasone (VAD). Results showed high complete remission (CR) rates of 19 percent in the VcD arm as induction therapy and 35 percent post-transplantation. These high CR rates contributed to 141 patients not requiring a second transplant. In addition, data showed 95 percent of patients in the VcD arm were alive at one year. The study was conducted by the Intergroupe Francophone du Myelome (IFM) cooperative group and Nantes University Hospital (France) and selected for an oral presentation at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois, May 30 - June 3, 2008.
"These updated results clearly confirm that the high CR rates with induction therapy improved post-transplantation outcomes, including a decrease in the need for second transplantation," said Professor Harousseau, M.D., Hotel-Dieu Hospital. "We also are encouraged by the promising survival data already seen to date. This VELCADE based therapy now could be considered the standard induction treatment pre-transplant to which other regimens, including novel agents, should be studied against."
VELCADE is under priority review with the Food and Drug Administration (FDA) for potential approval in newly diagnosed multiple myeloma. The PDUFA date is June 20, 2008. VELCADE is the market leader in relapsed multiple myeloma and mantle cell lymphoma (MCL).
"These data, as well as the results from multiple clinical trials continue to demonstrate the ability of VELCADE to deliver consistently high complete remission rates that lead to improved clinical benefit, including survival," said Nancy Simonian, M.D., Chief Medical Officer, Millennium. "The updated results from the IFM, combined with the pending approval by the FDA, bring us one step further in establishing VELCADE as the foundation of therapy for patients with newly diagnosed multiple myeloma."
Results from this large clinical trial were presented by Professor Harousseau. The VcD arm versus the VAD arm showed:
-- 95 percent of patients were alive at one year compared to 92 percent
-- A CR rate of 19 percent compared to 8 percent as induction therapy (p=0.0004)
-- A CR rate of 35 percent compared to 23 percent post-transplantation (p=0.0063)
-- 63 percent of patients did not require a second transplantation compared to 44 percent (p<0.0001)
Patients in the VcD arm received four cycles of VELCADE at 1.3 mg/m2 on days 1, 4, 8 and 11 of a 21-day cycle. Patients also received dexamethasone at 40 mg on days 1 through 4 during cycles one through four and on days 9 through 12 during cycles one and two only. The patients in the VAD arm were treated for four 28-day cycles with vincristine at 0.4 mg/m2 on days 1 through 4; adriamycin at 9 mg/m2 on days 1 through 4; and dexamethasone at 40 mg on days 1 through 4, days 9 through 12 during cycles one through four and on days 17 through 20 during cycles one and two only. Half of the patients in each arm received dexamethasone, cyclophosphamide, etoposide and cisplatinum (DCEP) consolidation pre-transplant. VcD was well tolerated with the incidence of grade 3 and grade 4 adverse events similar in each arm. Serious adverse events were slightly lower with VcD.
About Multiple Myeloma
Multiple myeloma is the second most common hematologic malignancy and although the disease is predominantly a cancer of the elderly (the median age of onset is 70 years), recent statistics indicate both increasing incidence and younger age of onset. In the U.S., more than 50,000 individuals have MM and 20,000 new cases are diagnosed each year. Worldwide there are approximately 74,000 new cases and over 45,000 deaths annually.
VELCADE is being co-developed by Millennium Pharmaceuticals, The Takeda Oncology Company, and Johnson & Johnson Pharmaceutical Research & Development, L.L.C. Millennium is responsible for commercialization of VELCADE in the U.S. and Janssen-Cilag is responsible for commercialization in Europe and the rest of the world. Janssen Pharmaceutical K.K. is responsible for commercialization in Japan. For a limited period of time, Millennium and Ortho Biotech Inc. are co-promoting VELCADE in the U.S. VELCADE is approved in 85 countries worldwide. More than 100,000 patients have been treated with VELCADE globally.
In the U.S., VELCADE is indicated for the treatment of patients with multiple myeloma who have received at least one prior therapy. VELCADE is also indicated for the treatment of patients with mantle cell lymphoma who have received at least one prior therapy. VELCADE is contraindicated in patients with hypersensitivity to bortezomib, boron or mannitol. VELCADE should be administered under the supervision of a physician experienced in the use of antineoplastic therapy. In the European Union and many other countries worldwide, VELCADE is approved for patients with multiple myeloma after first relapse.
Risks associated with VELCADE therapy include new or worsening peripheral neuropathy, hypotension observed throughout therapy, cardiac and pulmonary disorders, gastrointestinal adverse events, thrombocytopenia, neutropenia and tumor lysis syndrome. Women of childbearing potential should avoid becoming pregnant while being treated with VELCADE. Cases of severe sensory and motor peripheral neuropathy have been reported. The long-term outcome of peripheral neuropathy has not been studied in mantle cell lymphoma. Acute development or exacerbation of congestive heart failure, and/or new onset of decreased left ventricular ejection fraction has been reported, including reports in patients with few or no risk factors for decreased left ventricular ejection fraction. There have been rare reports of acute diffuse infiltrative pulmonary disease of unknown etiology such as pneumonitis, interstitial pneumonia, lung infiltration and Acute Respiratory Distress Syndrome in patients receiving VELCADE. Some of these events have been fatal. A higher proportion of these events have been reported in Japan. There have been rare reports of Reversible Posterior Leukoencephalopathy Syndrome (RPLS) in patients receiving VELCADE. RPLS is a rare, reversible, neurological disorder which can present with seizure, hypertension, headache, lethargy, confusion, blindness, and other visual and neurological disturbances. VELCADE is associated with thrombocytopenia and neutropenia. There have been reports of gastrointestinal and intracerebral hemorrhage in association with VELCADE. Transfusions may be considered. Complete blood counts (CBC) should be frequently monitored during treatment with VELCADE. Rare cases of acute liver failure have been reported in patients receiving multiple concomitant medications and with serious underlying medical conditions.
Integrated Safety Data: Safety data from Phase II and III studies of single-agent VELCADE 1.3 mg/m2/dose twice weekly for 2 weeks followed by a 10-day rest period in 1163 patients with multiple myeloma (N=1008) and mantle cell lymphoma (N=155) were integrated and tabulated. In these studies, the safety profile of VELCADE was similar in patients with multiple myeloma and mantle cell lymphoma. In the integrated analysis, the most commonly reported adverse events were asthenic conditions (including fatigue, malaise, and weakness) (64%), nausea (55%), diarrhea (52%), constipation (41%), peripheral neuropathy NEC (including peripheral sensory neuropathy and peripheral neuropathy aggravated) (39%), thrombocytopenia and appetite decreased (including anorexia) (each 36%), pyrexia (34%), vomiting (33%), and anemia (29%). Twenty percent (20%) of patients experienced at least 1 episode of >/= Grade 4 toxicity, most commonly thrombocytopenia (5%) and neutropenia (3%). A total of 50% of patients experienced serious adverse events (SAEs) during the studies. The most commonly reported SAEs included pneumonia (7%), pyrexia (6%), diarrhea (5%), vomiting (4%), and nausea, dehydration, dyspnea and thrombocytopenia (each 3%). Adverse events thought by the investigator to be drug-related and leading to discontinuation occurred in 22% of patients. The reasons for discontinuation included peripheral neuropathy (8%), asthenic conditions (3%) and thrombocytopenia and diarrhea (each 2%). In total, 2% of the patients died and the cause of death was considered by the investigator to be possibly related to study drug: including reports of cardiac arrest, congestive heart failure, respiratory failure, renal failure, pneumonia and sepsis.
For more information about VELCADE clinical trials, patients and physicians can contact the Millennium Medical Product Information Department at 1-866-VELCADE (1-866-835-2233).
Millennium Pharmaceuticals, The Takeda Oncology Company, a leading biopharmaceutical company based in Cambridge, Mass., markets VELCADE, a novel cancer product, and has a robust clinical development pipeline of product candidates. Millennium research, development and commercialization activities are focused in two therapeutic areas: oncology and inflammation. By applying its knowledge of the human genome, understanding of disease mechanisms and industrialized drug discovery platform, Millennium is developing an exciting pipeline of innovative product candidates. Additional information about Millennium is available through its website, www.millennium.com.
This press release contains "forward-looking statements," including statements about the Company's growth and development of products. Various important risks may cause the Company's actual results to differ materially from the results indicated by these forward-looking statements, including: adverse results in its drug discovery and clinical development programs; failure to obtain patent protection for its discoveries; commercial limitations imposed by patents owned or controlled by third parties; the Company's dependence upon strategic alliance partners to develop and commercialize products and services based on its work; difficulties or delays in obtaining regulatory approvals to market products and services resulting from its development efforts; product withdrawals; competitive factors; difficulties or delays in manufacturing the Company's products; government and third-party reimbursement rates; the commercial success of VELCADE and INTEGRILIN® (eptifibatide) Injection; achieving revenue consistent with internal forecasts; and the requirement for substantial funding to conduct research and development and to expand commercialization activities. The Company disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise.
Source: Millennium Pharmaceuticals
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